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Geldanamycin, a HSP90 inhibitor, attenuates the hypoxia-induced vascular endothelial
growth factor expression in pigment epithelium cells in vitro |
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| Geldanamycin, a HSP90 inhibitor, attenuates the hypoxia-induced vascular endothelial
growth factor expression in pigment epithelium cells in vitro |
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作者：Wen-Chua… 文章来源：Departments of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung,
Taiwan 点击数：6681 更新时间：2008/5/21 9:49:27 
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| Abstract
Hypoxia is the most common factor contributing to the pathogenesis of choroidal
neovascularization, which is the major cause for blindness and occurs in proliferative
diabetic retinopathy and age-related macular degeneration. The purpose of this study is to
investigate the role of retinal pigment epithelial (RPE) cells in the regulation of subretinal
neovascularization under hypoxia and the possible function of a heat shock protein 90
(HSP90) inhibitor, geldanamycin (GA), in the regulation of VEGF expression. An in vitro
hypoxic experimental model was used to mimic the ischemic microenvironment of RPE cells.
The cell growth was measured by proliferation assay and the morphological observation was
documented by microscope. The gene expression of VEGF, HSP70, HSP90?and HSP90?
were measured using semi-quantitative RT-PCR. The VEGF release from RPE cells were
detected by ELISA. No alteration in growth rate and cell morphology under 1% O2 condition
for 24h was noticed. The proangiogenic growth factor VEGF, but not bFGF, released from
hypoxia-treated cells were higher than that of normoxic control. A similar tendency of VEGF
gene expression, detected by RT-PCR, was noticed in hypoxia-treated cells. Heat shock
pretreatment elevated HSP70 and VEGF gene expression and augmented the
hypoxia-induced VEGF gene expression and protein release. Pretreatment with GA can
significantly suppress the hypoxia-induced VEGF gene expression in and peptide release
from RPE cells. This in vitro finding suggests that HSP90 inhibitors could be considered as a
novel anti-angiogenesis agent for diseases with intraocular neovascularization. |
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